Human papillomavirus infection and primary fallopian tube carcinoma: a seroepidemiological study.

OBJECTIVE: To evaluate the role of human papillomavirus (HPV) types 6, 11, 16, 18, 31 or 33 infection in primary fallopian tube carcinoma (PFTC). DESIGN: A retrospective case-control study. SETTING: Department of Obstetrics and Gynaecology, Helsinki University Hospital, Finland. POPULATION: Seventy-eight consecutive women with PFTC diagnosed between 1985 and 2000 were studied. For each case, two healthy controls were selected. METHODS: Serum immunoglobulin G antibodies to HPV types 6, 11, 16, 18, 31 and 33 were measured from women with PFTC and their healthy controls. MAIN OUTCOME MEASURES: Analysis of HPV 6, 11, 18, 31 and 33 seropositivity among women with PFTC and controls. RESULTS: Seropositivity rates of non-oncogenic or oncogenic HPV types did not differ between cases and controls, odds ratios being 1.04-1.30 for oncogenic HPVs and 1.08-1.19 for non-oncogenic HPVs, similarly. We did not find any multiplicative joint effect in PFTC by antibodies to more than one oncogenic HPV type; neither did we find any antagonistic effect among women with antibodies to non-oncogenic and oncogenic HPV types. CONCLUSIONS: Our results do not suggest any link between PFTC and serological evidence for HPV infection.

Past chlamydial infection is not associated with primary fallopian tube carcinoma.

We conducted a retrospective seroepidemiological study to evaluate the relationship between past chlamydial infection and primary fallopian tube carcinoma (PFTC). Postoperative serum samples were drawn from 79 consecutive patients treated for PFTC in 1985-2000. For each case two controls were selected. Serum samples were analysed for IgG antibodies to different C. trachomatis serotype pools and to C. pneumoniae. Seropositivity in general or serum antibody levels to different C. trachomatis serovars or C. pneumoniae did not differ between PFTC patients and controls. The lack of association between anti-chlamydial antibodies and PFTC suggests that past chlamydial infection does not play a role in the etiopathogenesis of PFTC. However, because chlamydial infection is common at young age and PFTC develops decades later, we cannot definitively exclude the possibility that C.trachomatis contributes to the development of PFTC.

Preoperative serum hCGbeta as a prognostic marker in primary fallopian tube carcinoma.

OBJECTIVES: It was the aim of this study to evaluate the prognostic value of the pretreatment serum concentrations of the beta-subunit of human chorionic gonadotropin (hCGbeta), CA 125 and tumour-associated trypsin inhibitor (TATI) in primary fallopian tube carcinoma (PFTC). METHODS: The pretreatment serum concentrations of hCGbeta, CA 125 and TATI were analyzed in serum samples from 60 women with a mean age of 61 years, treated for PFTC between 1985 and 2000. Of the 91 patients treated during this period, 31 were excluded because no serum sample was available. The patients were followed-up for recurrence and survival until February 14, 2003. The prognostic value of the serum markers were compared with those of stage, grade and histological type. RESULTS: The median survival time was 27 months and the overall 5-year survival rate 33%. Stage and size of the residual tumour (<1 vs. > or =1 cm) predicted both overall and disease-free survival (p < 0.050). Histology (serous vs. others) (p = 0.023) also influenced overall survival. Overall 5-year survival was 38% when serum hCGbeta was below 3.5 pmol/l, while it was 18% when the level was higher (p = 0.052). The corresponding disease-free 5-year survival was 38 and 20%, respectively (p = 0.014). Patients with CA 125 values above 1,017 kU/l had an overall 5-year survival of 39% as compared with 14% for those with lower values (p = 0.009), while the disease-free survival was 37 and 23%, respectively (p = 0.096). Serum TATI was not a prognostic marker. Serum concentrations of hCGbeta and CA 125 correlated significantly with stage (p = 0.049 and p = 0.050, respectively). In multivariate Cox proportional hazards regression analysis, only hCGbeta, stage and histology emerged as independent prognostic factors. CONCLUSIONS: Clearly elevated serum concentrations of hCGbeta and CA 125 predict survival in fallopian tube carcinoma, but in multivariate analyses, only hCGbeta is a prognostic factor independent of stage and histology.

Type IV collagen in the basal membrane of human papillomavirus associated premalignant and malignant squamous cell lesions of the uterine cervix.

In the present study, the expression of type IV collagen associated with the basal membrane (BM) was studied histochemically (indirect immunoperoxidase-antiperoxidase) in cervical human papillomavirus (HPV) lesions (diagnosed using in situ DNA hybridization) of different grades. The expression of type IV collagen in premalignant epithelial lesions (HPV with and without cervical intraepithelial neoplasia) was identical with that in the BM of normal exocervical epithelium, in contrast to 60% (3/5) of carcinoma in situ lesions and 90% (10/11) of invasive carcinomas, where the staining pattern was interrupted and the staining intensity reduced. Thus, the expression of type IV collagen seems to remain unchanged during the entire spectrum of premalignant stages of cervical HPV lesions. This suggests that the squamous epithelial cells responsible for the formation of the BM are not affected by this virus at early stages of the disease, and immunohistochemical recognition of an intact staining pattern of type IV collagen may signify well-preserved basal cell function (confined to nonmalignant?) HPV-infected squamous epithelium.

Immunization of chickens via the bursa of Fabricius isolated from the rest of the gut-associated lymphoid tissue using four surgical techniques.

To study the role of the chicken bursa of Fabricius separately from the rest of the gut-associated lymphoid tissue (GALT), four operating methods were developed; these techniques are described in detail. Bursal function and immunological state of the operated chickens were assessed by applying colloidal carbon, Brucella abortus organism, and sheep red blood cells (SRBC) into the isolated bursa and then measuring the humoral immune responses. Closing the bursal duct, after administering antigens through it, was shown to be a reliable and reproducible method for immunizing chickens strictly via the bursal system. In this method, morphology and endocytosis of carbon in the isolated bursae were normal. Furthermore, the anti-Brucella titers did not significantly differ from those in the unoperated per anum immunized control chickens, whereas the response to SRBC was significantly lower (P less than .001) in the operated chickens compared with controls. Separation of the bursa from the rest of the GALT showed that the chicken bursa of Fabricius functions as a peripheral lymphoid organ; specific antibodies are formed against antigens introduced into the bursal lumen. The operating method also has confirmed that Brucella is a bursa-dependent antigen, but that SRBC need cooperation of the GALT to evolve a good humoral immune response.

Effect of a sport drink mixture with and without addition of fluoride and magnesium on plaque formation, dental caries and general health of rats.

A sport drink mixture (pH 3.2) containing 6% sucrose was given to Osborne-Mendel rats for 42 days. In some experimental groups the drink was supplemented with 15 ppm F, 38.5 ppm Mg or both F and Mg. The rats were fed a slightly cariogenic powdered diet containing 15% sucrose. Sport drink mixture increased significantly the accumulation of plaque but, compared with a group that drank distilled water, did not affect caries. Addition of fluoride to the sport drink mixture, alone or with magnesium, significantly reduced caries and tended to decrease plaque; addition of magnesium had no clear effect on plaque or caries. In spite of the fact that the rats had a sport drink mixture as the only drink for 6 wk, there were no untoward effects on growth, in histological studies of the inner organs, or in Ca, Mg, Na and K contents of kidney, heart and aorta.

Lingua fissurata. A clinical, stereomicroscopic and histopathological study.

The purpose of this study was to describe clinical, stereomicroscopic and light microscopic findings for fissured tongue in 17 patients and compare them with 17 normal controls. Clinical symptoms were found in 13 of 17 patients who complained of scoreness of the tongue. Usually the symptoms lasted more than 3 years. In 15 cases, fissures involved the entire tongue, while in 2 cases, only the edges of the tongue were affected. In all patients, papillae of varying sizes were found in the area of fissures. The papillae were easily noted using stereomicroscopy on fixed-tissue specimens, but could also be seen with the naked eye during careful clinical examinations. Light microscopic studies indicated that the number of inflammatory cells was far greater in the mucosa of fissured tongues than in normal tongues, and this inflammation was not confined only to the fissures. The rete pegs of the epithelium were longer in fissured tongues than in normal tongues, 800 (+/- 79) micron and 620 (+/- 69) micron, respectively, (p less than 0.001). The lamina propria was also thicker in fissured tongues than in normal tongues, 390 (+/- 74) micron and 170 (+/- 61) micron, respectively, (p less than 0.001). In normal tongues, keratohyaline granules were observed in the filiform papillae around the area of hairs but these granules were absent in fissured tongues.

A scanning electron microscopic study of fissured tongue.

In this study, scanning electron microscopy was used to describe the surface morphology of fissured tongue. Tissue samples from the anterior part of the tongue were taken from 15 patients with fissured tongue. The formalin-fixed samples were processed routinely for scanning electron microscopy. Typically, the surface of a fissured tongue was covered with hairless papillae of various sizes. The biggest papillae were larger than the body of a normal filiform papilla, and the apex was rounded and rough. On the other hand, some of these papillae had a few hairs and resembled normal filiform papillae, but were flatter. In addition some papillae formed only slight elevations on the tongue mucosa, which was smooth and contained some desquamating cells. The walls of the fissure found in macroscopical examination consisted of very low elevations of the smooth mucosa with some desquamating cells. At high magnification the superficial cells of the epithelium were polygonal. On their surface there were branching or parallel microplicae, which were often broken. Only occasionally superficial cells of the large papillae had a pitted appearance. The knob-like structures found among the microplicae and small cracks between the epithelial cells are discussed from the standpoint of the pathogenesis of fissured tongue.

Changes in composition of whole saliva in patients with fissured tongue.

Both resting and paraffin-stimulated whole saliva were studied in 25 patients with fissured tongue and in their age and sex-matched healthy controls. The groups did not differ in dental or periodontal health. No significant differences were found between the groups in the salivary secretion rate, pH and buffer capacity, or in the frequency of lactobacilli and yeasts in saliva samples and scrapings from tongue surface. In patients with fissured tongue, unstimulated whole saliva displayed significantly elevated levels of sodium, lysozyme, myeloperoxidase and all immunoglobulins (isotypes A, G and M) when compared with the controls. These changes most likely reflect the inflammation frequently seen in the biopsies of fissured tongue. No differences between the groups existed in the amounts of salivary potassium, calcium, inorganic phosphate, amylase and total protein. Our study shows that in patients with fissured tongue the salivary secretion and composition are normal. However, components from plasma and inflammatory cells are diagnostically elevated in the whole saliva samples of patients with fissured tongue when compared with the healthy controls.

A scanning electron microscopic study of the dorsal surface of the human tongue.

To study the dorsal surface of the human tongue using a scanning electron microscopy (SEM), tissue specimens were taken from the anterior part of the tongues of 15 individuals aged from 21- to 28-years-old. The formalin-fixed samples were processed routinely for SEM. With SEM the surface of the normal tongue mucosa was shown to be rather evenly covered by filiform papillae, with some fungiform papillae scattered among them. Filiform papillae consisted of two parts: the body and hairs. The mucosal surface of the body was smooth; the squamous epithelial cells were polygonal, and their boundaries were prominent. On the surface of the superficial epithelial cells were parallel or branching microplicae. Each filiform papilla had 6-10 hairs, which were scaled and covered by an extensive plaque of microorganism. The upper surface of the fungiform papillae was smooth; only a few desquamating cells were seen. The superficial cells had a pitted appearance and cell boundaries overlapped. Taste pores, up to 3 pores in a single papilla, were found on the upper surface. Desquamation was more pronounced on the base of the fungiform papillae than on the upper surface. In almost all fungiform papillae some hairs protruded from the base. Parallel microplicae were found on the surface of the superficial cells of the base. The structure and function of the human tongue, as well as the microplicae of its superficial cells, are compared to those of various species of animals.

Involution of the chicken bursa of Fabricius: a light microscopic study with special reference to transport of colloidal carbon in the involuting bursa.

The involution of the bursa of Fabricius in White Leghorn chickens and the transport of colloidal carbon in the involuting bursa were studied on light microscopy. In chickens, from newly hatched to 23.5 weeks of age, the bursa was weighed, its histology was described, and the mitoses in the cortical and medullary compartments of the lymphoid follicles were counted. Decrease in bursal weight and in the number of mitoses were observed between 10 and 16 weeks of age. During week 17.5, the follicle-associated epithelium began to lose its endocytic capability, and mucin droplets appeared in the follicular medulla initiating the large mucoid cysts that were seen in the later phases of involution. The involutionary process was almost completed by week 23.5, when the bursa appeared as a fibrotic residue without intact lymphoepithelial structures. The particulate tracer used, colloidal carbon, was not observed to be transported to other organs from the bursa. The present study gives further support to the idea that after completing its central immune function in 6 weeks [21] the bursa, as estimated histologically, still possesses capacity to function like a peripheral lymphoid organ until 16 weeks of age.

Thymus-dependent immune functions in chickens bursectomized with colchicine applied to the anal lips.

Thymus-dependent immune functions were investigated in chickens bursectomized neonatally with colchicine solution given per anum. Antibody responses to thymus-dependent antigens sheep red blood cells (SRBC) and human gamma-globulin (HGG) were delayed, reaching the normal level after the third antigen stimulation. Also the mitogenic responses of peripheral blood lymphocytes were preserved, and no changes in the thymic morphology were found. In contrast, antibody responses to bursa-dependent antigen Brucella abortus were low and the switch of immunoglobulin isotypes from IgM to IgA and IgG was disturbed. It can be concluded that neonatal bursectomy with cloacal administration of colchicine does not significantly affect T cell functions, whereas B cell functions are partially deficient.

Monoclonal gammopathy with neurological signs and symptoms. A clinical, neurophysiological and muscle biopsy study.

Clinical, neurophysiological and muscle biopsy findings in ten patients with monoclonal gammopathy are reported. Three patients had polyneuropathy, one had hemiparkinsonism, one migraine and radicular symptoms and one paresthesiae and radicular symptoms. Amyloidosis was not found in muscle biopsy specimens. All but one patient with neurological findings also had positive immunofluorescence staining for tissue-bound immunoglobulins in muscle biopsy specimens. The tissue-bound immunoglobulins usually belonged to the same class as the M-component. None of the biopsies of patients without neurological findings were positive.

Electroneuromyographical and morphological findings in progressive myoclonus epilepsy (PME).

The purpose of this study was to assess the function of peripheral nerves and muscles and to describe morphological changes in muscle biopsies of patients with progressive myoclonus epilepsy. Electroneuromyographic studies were performed on 24 adult patients whose mental and motor skills were either little, moderately or severely impaired by the disease. In 5 patients a specimen of tibial anterior muscle was morphologically and histochemically investigated. The electrophysiological functions of the peripheral nerves and muscles showed gradual increasing abnormalities parallel to the severity of clinical deterioration. The muscle biopsies of 2 patients showed signs compatible with peripheral neuropathy. These findings suggested that progressive myoclonus epilepsy may be related to a systemic membrane disorder.

Morphological and histochemical characterization of the medullary cells in the bursal follicles of the chicken.

Using light and electron-microscopy and enzyme-histochemical methods the cells in the follicular medulla of the chicken bursa of Fabricius were characterized. The following cell types were identified: lymphocytes of both B and T cell series, lymphoblasts, plasma cells, dendritic reticulum cells and histiocytic reticulum cells--the latter being the only cells phagocytosing the tracer substance used (colloidal carbon). The medullary cells observed showed electron-microscope and histochemical characteristics typical of the germinal center cells in mammalian lymphoreticular tissues. Furthermore, a distinct bursal follicular epithelial cell was identified, and so was a medullary epithelial structure resembling Hassall's corpuscle of the thymus. These findings give further support to the idea that the avian bursa has functions of a peripheral lymphoid organ as well as containing T-derived lymphocytes.

Elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxine in goat milk.

2,3,7,8-Tetrachlorodibenzo-p-dioxine (TCDD) 200 ng/day, was given orally to 7 goats for 2 months, followed by an elimination period of 1 month. Then a daily dose of 400 ng TCDD was given for 1 month to the same animals. Two animals were killed and the rest of the animals were observed for several months. The excretion of TCDD in milk was studied by glass capillary gas fragmentography, where the minimal detectable concentration was below 5 ppt. After the first feeding the concentration of TCDD in milk achieved a maximum of 20.8 +/- 6.6 ppt while a similar value of 19.3 +/- 6.6 ppt was observed after the second feeding. After this period, the concentration of TCDD decreased slowly with values, after 18 weeks, of 4, 2 +/-, 3 and 6 ppt. The concentration of TCDD in the liver in the two animals killed was 1039.0 and 898.0 ppt. There were no differences in clinical observations or blood and urine analyses when experimental animals were compared with controls.

Humoral immunodeficiency in chickens induced by chemical bursectomy with colchicine applied on the anal lips.

Colchicine was applied on the anal lips of chickens on 4 consecutive days after hatching. At the ages of 4 and 10 weeks the agglutinin responses to Brucella abortus and to sheep red blood cells (SRBC) after intraperitoneal and per anum immunization were decreased in these animals. IgG and IgM antibodies to Brucella, measured by enzyme-linked immunosorbent assay (ELISA), were also diminished in 12-week-old chickens. The total concentration of plasma IgG, measured by the ELISA-inhibition method, was diminished whereas the IgM level was not influenced by the colchicine treatment. These results broadly resemble the findings after surgical bursectomy or cyclophosphamide treatment. It can be concluded that colchicine applied on the anal lips of chickens causes a long-lasting deficiency of humoral immunity and thus seems to be a useful new tool in the exploration of the humoral-immune functions of the chickens.

A morphometrical study of chicken spleen with special reference to the bursa dependence of the white pulp.

Histoquantitative methods were applied to the study of the bursa dependence of the while pulp structures of normal chickens and chickens bursectomized neonatally by surgical means or chemically by the anal application of colchicine solution. The morphometrical analysis of the spleens from 6- and 12-week-old bursectomized chickens showed that the amount of the white pulp tissue and its compartments, periellipsoidal lymphoid tissue (PELT), periarteriolar lymphoid tissue (PALT) as well as the number of the germinal centers (GC), were decreased, when compared to the controls. The perivenous lymphoid tissue (PVLT) seemed not to be affected by the bursectomies. The results indicate that the PELT, PALT and GCs are bursa-dependent structures of chicken spleen, whereas the PVLT seems to be bursa-independent.

Late effects of colchicine on the bursa of Fabricius after neonatal application on the anal lips of chickens.

One week after the application of colchicine on the anal lips of chickens, the bursa of Fabricius was devoid of lymphoid cells and contained only a few epithelial buds, all of which were later repopulated with lymphoid cells to form mature lymphoid follicles. After the intraperitoneal injection of cyclophosphamide, numerous epithelial buds were found in the bursa, and at the age of six weeks only a few of them were populated with lymphoid cells. On week 6, the bursal weights of the chickens treated with colchicine were only about 10% of the normal, and about 80% of the bursal weights of the cyclophosphamide-treated chickens. The colchicine treatment affected the morphology of the spleen less than the treatment with cyclophosphamide. It is concluded that this new model of chemical bursectomy differs distinctly from the cyclophosphamide model and therefore serves as a new tool in studying bursal function in chicken.